Enalapril Maleate

Trade Names:Vasotec- Tablets 2.5 mg- Tablets 5 mg- Tablets 10 mg- Tablets 20 mg

Trade Names:Vasotec IV- Injection 1.25 mg enalaprilat/mL

Pharmacology

Competitively inhibits angiotensin I-converting enzyme, preventing conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that also stimulates release of aldosterone. Results in decrease in BP, reduced sodium absorption, and potassium retention.

Pharmacokinetics

Absorption

Bioavailability is approximately 60%. T _max is within 1 h (enalapril); 3 to 4 h (enalaprilat).

Distribution

Enalapril crosses the blood-brain barrier poorly, if at all. Enalaprilat does not cross the blood-brain barrier.

Metabolism

Enalapril is a prodrug and is hydrolyzed to enalaprilat (more potent than enalapril).

Elimination

Intact enalapril and approximately 40% of the dose as enalaprilat is excreted in the urine. Approximately 94% is recovered in the urine and feces. The t _½ is 1.3 h (enalapril). Enalaprilat is dialyzable.

Onset

1 h.

Peak

4 to 6 h.

Duration

At least 24 h.

Special Populations

In those with glomerular filtration rate 30 mL/min or less, the peak and trough enalaprilat levels increase, T _max increases, and time to steady state may be delayed. Dosage adjustment recommended.

Indications and Usage

Treatment of hypertension and symptomatic CHF in combination with diuretics and digitalis and asymptomatic left ventricular dysfunction.

Unlabeled Uses

Treatment of diabetic nephropathy, childhood hypertension, hypertension related to scleroderma, and renal crisis scleroderma.

Contraindications

History of angioedema related to previous treatment with an ACE inhibitor and in patients with hereditary or idiopathic angioedema; hypersensitivity to ACE inhibitors.

Dosage and Administration

PO Initial dose: 2.5 mg twice daily. Usual dose: 2.5 to 20 mg/day in 2 divided doses (max, 40 mg/day). Titrate doses upward as tolerated over a period of a few days or weeks. The max daily dose is 40 mg in divided doses.

IV Hypertensive patients at risk (eg, those with heart failure, hyponatremia, high-dose diuretic therapy, recent intensive diureses or increase in diuretic dose, renal dialysis, or severe volume or salt depletion of any etiology) have potential for extremely hypotensive response. Initiate therapy under very close medical supervision. The starting dose should be 0.625 mg or less administered IV over a period of 5 min or more and preferably longer (up to 1 h).

PO Initial dose: 2.5 to 5 mg/day. Titrate to desired BP control. Usual maintenance dose: 10 to 40 mg/day in single or twice daily doses. IV 1.25 mg over a 5-min period every 6 h. For patients with Ccr of 30 mL/min or less, the dose is 0.625 mg. Dose may be repeated if after 1 h the clinical response is inadequate. Additional doses of 1.25 mg may be administered at 6-h intervals. For dialysis patients, the initial dose is 0.625 mg or less given over 5 min or preferably longer (up to 1 h).

PO Initial dose: 0.08 mg/kg (up to 5 mg) every day. Adjust dose according to BP response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients.

PO Initial dose: 2.5 mg twice daily. Titrate to targeted daily dose of 20 mg in divided doses.

PO Titrate dosage upward until BP is controlled or until a max dosage of 40 mg/day is reached. Use an initial dosage of 5 mg/day in normal renal function and mild impairment (Ccr more than 30 mL/min); 2.5 mg/day in moderate to severe renal function impairment (Ccr 30 mL/min or less); and 2.5 mg on the day of dialysis in dialysis patients (adjust dosage on nondialysis days based on BP response).

General Advice

• Give without regard to meals. Administer with food if GI upset occurs.
• Tablets may be mixed with Bicitra and Ora-Sweet SF , following manufacturer's guidelines, to form a suspension.
• Shake well before measuring dose.
• Administer prescribed dose using cup, spoon, or syringe.

• For IV administration only when oral therapy is not practical. Not for intradermal, subcutaneous, or IM administration.
• May be administered undiluted or mixed with up to 50 mL of D5W, NS, D5WNS, or D5W in Lactated Ringer's injection. Dilution is stable for up to 24 h at room temperature.
• Do not administer if particulate matter, cloudiness, or discoloration is noted.

Storage/Stability

• Store tablets at controlled room temperature (59° to 89°F). Protect from moisture.
• Store suspension in refrigerator (36° to 46°F). Discard any unused suspension after 30 days.
• Store injection at controlled room temperature (59° to 89°F).

Drug Interactions

Greater risk of hypersensitivity possible with coadministration.

Enalapril bioavailability may be decreased. Separate administration times by 1 to 2 h.

Cough may be exacerbated.

May increase or decrease plasma levels of digoxin.

Hypotensive effects may be reduced, especially in low-renin or volume-dependent hypertensive patients.

Increased lithium levels and symptoms of lithium toxicity may occur.

May increase pharmacologic effect of enalapril.

May increase serum potassium levels.

Pharmacologic effects of enalapril may be decreased.

Laboratory Test Interactions

False elevation of liver enzymes or serum bilirubin may occur.

Adverse Reactions

Cardiovascular

Hypotension (7%); angina, chest pain, orthostatic hypotension, syncope (2%); myocardial infarction (1%); tachycardia (less than 1%).

CNS

Headache (5%); dizziness (4%); fatigue (3%); vertigo (2%); asthenia (1%).

Dermatologic

Rash (1%); photosensitivity (less than 1%).

GI

Abdominal pain, diarrhea (2%); nausea, vomiting (1%).

Genitourinary

UTI (1%).

Hematologic

Decreased hemoglobin and hematocrit, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, eosinophilia.

Metabolic

Hyperkalemia.

Respiratory

Bronchitis, cough, dyspnea (1%).

Precautions

Pregnancy

Category D (second, third trimester); Category C (first trimester).

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in pediatric patients younger than 1 mo of age, neonates, or pediatric patients with glomerular filtration rate less than 30 mL/min/1.73 m ² (oral). Safety and efficacy not established (IV).

Renal Function

Reduce dose and give less frequently. In renal function impairment, stable elevations in BUN and serum creatinine may occur because of inadequate renal perfusion; monitor renal function during first few weeks of therapy and adjust dosage.

Angioedema

May occur. Use drug with extreme caution in patients with hereditary angioedema.

Aortic stenosis/hypertrophic cardiomyopathy

As with other vasodilators, enalapril should be used with caution in patients with obstruction in the outflow tract of the left ventricle.

Cough

Chronic dry cough may occur during treatment; higher incidence in women.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.

Hypotension/first-dose effect

Significant decreases in BP may occur after first dose, especially in severely salt- or volume-depleted patients or in those with heart failure; monitor closely for 2 h or more after initial dose and during first 2 wk of therapy. Minimize risk by discontinuing diuretics, decreasing dose, or increasing salt intake approximately 1 wk prior to initiating enalapril.

Neutropenia and agranulocytosis

Have occurred; risk appears greater with renal dysfunction, heart failure, or immunosuppression; monitor WBC counts frequently.

Overdosage

Symptoms

Hypotension.

Patient Information

• Injection
• Advise patient that medication will be prepared and administered by a health care professional in a medical setting.

• Tablets and Suspension
• Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
• Advise patient to try to take each dose at about the same time each day.
• Advise patient or caregiver to shake suspension well before measuring each dose.
• Inform hypertensive patient that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
• Caution patient not to change the dose or stop taking unless advised by health care provider.
• Instruct patient to continue taking other medications for the condition as prescribed by health care provider.
• Instruct patient in BP and pulse measurement skills.
• Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
• Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
• Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
• Emphasize to hypertensive patient the importance of other modalities on BP control: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
• Emphasize to heart failure patient the importance of other modalities that can help control heart failure symptoms: weight control, progressive exercise program, smoking cessation, and moderate intake of alcohol and salt.
• Advise heart failure patient to weigh daily, keep a record of daily weights, and notify health care provider if rapid weight gain (eg, 5 pounds in 1 wk) is noted or if edema or shortness of breath are getting worse.
• Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP resulting in lightheadedness or fainting.
• Advise patient that medication may cause dizziness or lightheadedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
• Instruct patient to stop taking drug and immediately report any of these symptoms to health care provider: sore throat, fever, swelling of the hands or feet, irregular heartbeat, chest pains, fainting, swelling of the face, lips, eyelids, or tongue, difficulty breathing.
• Instruct patient to inform health care provider if a persistent cough develops while taking this medication.
• Caution patient not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by health care provider.

Copyright © 2009 Wolters Kluwer Health.